@article {Oberhuber770701, author = {Monika Oberhuber and Matteo Pecoraro and Mate Rusz and Georg Oberhuber and Maritta Wieselberg and Peter Haslinger and Elisabeth Gurnhofer and Jan Pencik and Robert Wiebringhaus and Michaela Schlederer and Theresa Weiss and Margit Schmeidl and Andrea Haitel and Marc Brehme and Wolfgang Wadsak and Johannes Griss and Thomas Mohr and Alexandra Hofer and Anton J{\"a}ger and Gerda Egger and J{\"u}rgen Pollheimer and Gunda Koellensperger and Matthias Mann and Brigitte Hantusch and Lukas Kenner}, title = {STAT3-dependent systems-level analysis reveals PDK4 as an independent predictor of biochemical recurrence in prostate cancer}, elocation-id = {770701}, year = {2019}, doi = {10.1101/770701}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Prostate cancer (PCa) has a broad spectrum of clinical behaviour, hence biomarkers are urgently needed for risk stratification. We previously described the protective effect of STAT3 in a prostate cancer mouse model. By utilizing a gene co-expression network in addition to laser microdissected proteomics from human and murine prostate FFPE samples, we describe STAT3-induced downregulation of the TCA cycle/OXPHOS in PCa on transcriptomic and proteomic level. We identify pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of the TCA cycle, as a promising independent prognostic marker in PCa. PDK4 predicts disease recurrence independent of diagnostic risk factors such as grading, staging and PSA level. Furthermore, PDK4 expression is causally linked to type 2 diabetes mellitus, which is known to have a protective effect on PCa. We conclude that this effect is related to PDK4 expression and that PDK4 loss could serve as a biomarker for PCa with dismal prognosis.}, URL = {https://www.biorxiv.org/content/early/2019/09/19/770701}, eprint = {https://www.biorxiv.org/content/early/2019/09/19/770701.full.pdf}, journal = {bioRxiv} }